Origins of Stereoselectivity in Peptide-Catalyzed Kinetic Resolution of Alcohols

The origin of the stereoselectivity of the tetrapeptide-catalyzed kinetic resolution of trans-2-N-acetamidocyclohexanol is investigated by means of density functional theory calculations. Transition states for the functionalization of both (R,R) and (S,S) substrates were optimized considering all possible conformers. Due to the flexibility of the peptidic catalyst, a large number of transition states had to be located, and analysis of the geometries and energies allowed for the identification of the main factors that control the stereoselectivity.